Managing chronic myeloid leukemia for treatment-free remission: a proposal from the GIMEMA CML WP

Several papers authored by international experts have proposed recommendations on the management of BCR-ABL1+ chronic myeloid leukemia (CML). Following these recommendations, survival of CML patients has become very close to normal. The next, ambitious, step is to bring as many patients as possible into a condition of treatment-free remission (TFR). The Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA; Italian Group for Hematologic Diseases of the Adult) CML Working Party (WP) has developed a project aimed at selecting the treatment policies that may increase the probability of TFR, taking into account 4 variables: the need for TFR, the tyrosine kinase inhibitors (TKIs), the characteristics of leukemia, and the patient. A Delphi-like method was used to reach a consensus among the representatives of 50 centers of the CML WP. A consensus was reached on the assessment of disease risk (EUTOS Long Term Survival [ELTS] score), on the definition of the most appropriate age boundaries for the choice of first-line treatment, on the choice of the TKI for first-line treatment, and on the definition of the responses that do not require a change of the TKI (BCR-ABL1 6410% at 3 months, 641% at 6 months, 640.1% at 12 months, 640.01% at 24 months), and of the responses that require a change of the TKI, when the goal is TFR (BCR-ABL1 >10% at 3 and 6 months, >1% at 12 months, and >0.1% at 24 months). These suggestions may help optimize the treatment strategy for TFR

New mechanical model to predict the load bearing resistance of shear connectors with modern forms of profiled sheeting

The rules in EN1994-1-1 concerning the resistance of shear connections in composite beams with headed shear studs and steel sheeting relies on push-out tests, which have been performed between the late seventies and the early nineties of the last century. In the recent years, new geometries of metal decking have appeared on the market with the target to reduce the volume and weight of the concrete slab and to maximise the slab efficiency. The influence of these new geometries on the load bearing behaviour of shear connections has to be verified. Amongst others, the RFCS research project DISCCO investigated the shear stud resistance in combination with such novel steel decking. It turned out that, the current EN 1994-1-1 rules need to be modified especially for metal decking with narrow and deep deck ribs. Alternative analytical equations for the estimation of the shear resistance have been derived and statistically evaluated according to EN 1990. Details are presented in this contribution

New mechanical model to predict the load bearing resistance of shear connectors with modern forms of profiled sheeting

The rules in EN1994-1-1 concerning the resistance of shear connections in composite beams with headed shear studs and steel sheeting relies on push-out tests, which have been performed between the late seventies and the early nineties of the last century. In the recent years, new geometries of metal decking have appeared on the market with the target to reduce the volume and weight of the concrete slab and to maximise the slab efficiency. The influence of these new geometries on the load bearing behaviour of shear connections has to be verified. Amongst others, the RFCS research project DISCCO investigated the shear stud resistance in combination with such novel steel decking. It turned out that, the current EN 1994-1-1 rules need to be modified especially for metal decking with narrow and deep deck ribs. Alternative analytical equations for the estimation of the shear resistance have been derived and statistically evaluated according to EN 1990. Details are presented in this contribution

Germline prokineticin receptor 2 (PROKR2) variants associated with central hypogonadism cause differental modulation of distinct intracellular pathways

Defects of prokineticin pathway affect the neuroendocrine control of reproduction, but their role in the pathogenesis of central hypogonadism remains undefined, and the functional impact of the missense PROKR2 variants has been incompletely characterized